In the field of mammalian reproduction, many diagnostic procedures exist to aid the reproduction practitioner in making a diagnosis and choosing an appropriate course of action.
Currently, infertility in humans is defined as one year of unprotected coitus without conception. Approximately 10-15% of couples are affected by infertility. The risk of infertility is doubled for women between the ages of 35 to 44 as compared to women between the ages of 30 and 34. Approximately 600,000 couples sought professional help during the year 1968. However, in the early 1980's this number increased to over 2 million visits per year for infertility. Changes in fertility patterns will have a significant impact on the make-up of populations. It has been calculated that by the middle of the next century, the population in the United States will decline without immigration. Furthermore, the percent of people over the age of 65 will increase to over 23% in the next 100 years, resulting in an older and smaller work force.
In the United States, the majority of infertility can be accounted for by problems in the female. Evaluating a female for infertility can be complex. Examination of the fallopian tubes is an important early step in mammalian fertility evaluation due to the increased evidence of pelvic inflammatory disease. Currently, a hysterosalpingogram (HSG) is the procedure of choice to examine the patency of the fallopian tubes. In addition to HSG, hysteroscopy which is the direct examination of the uterus by a fiber optic device, is important to determine the presence of endometrial polyps, submucous leiomyomas, and other abnormalities within the uterus itself.
Another category of diagnostic procedures includes examination of ovarian function including ovulation and the secretion of progesterone during the luteal phase of the menstrual cycle. Ovarian function can be crudely assessed by measuring basal body temperatures during the menstrual cycle and cervical mucous testing around the time of ovulation. More accurate testing can be performed by measuring luteinizing hormone, a pituitary hormone which induces ovulation after a mid-cycle surge. Finally, serum progesterone levels can be measured to assess for normal luteal phase of the menstrual cycle.
The endometrium itself can be directly assessed by performing an endometrial biopsy three days before the suspected onset of menses. In assessing a mammalian endometrium, current gynecology and infertility physicians depend on pathologists to examine endometrial biopsies by hematoxylin and eosin staining of paraffin embedded specimens. For infertility patients, the reading of these biopsies provides information about the day of the cycle following ovulation, the adequacy of the luteal phase, and other potential data, such as infection, inflammation, or neoplasia of the endometrium. However, in most cases there is no evaluation of the functional and biochemical quality of the endometrium, and often no histologic reading to explain a patient's infertility problem.
Finally, the infertility patient could undergo endoscopic examination through an incision in the abdomen to directly visualize the external surfaces of the ovary, fallopian tubes and uterus to visualize any gross pathology which was not detected by previous examinations.
A high percentage of women who are unable to carry a pregnancy to full term undergo spontaneous abortion generally within the first six weeks. Pregnancy loss during the first six weeks has been shown to be as high as between 15 and 20%. Furthermore, the chance of a successful live birth after consecutive abortions without a live birth is only 40-50%.
In vitro fertilization (IVF) requires the removal of ova from a mammalian ovary, and exposure of these ova to sperm outside the body. Fertilization of each ovum requires that at least one living sperm penetrates the zona pellucida (outer covering) of the ovum and fuses with the pronucleus. Once this has occurred and the ova are fertilized, they can be transferred to a uterus where they can become implanted on the uterine wall. If implantation occurs, the pregnancy can proceed as if fertilization had occurred within the body. In vitro fertilization has gained widespread professional and public acceptance. However, despite the ever increasing frequency and refinement of this procedure, in vitro fertilization attempts most often do not result in pregnancy. In vitro pregnancy rates are currently only about 15 to 20 percent. For a variety of reasons, exposing the ova to sperm does not necessarily result in fertilization. Furthermore, even where the ova is fertilized, the placement of the ova in a uterus usually does not result in normal implantation. The low success rate of IVF often leads to an excessive financial and psychological burden for the infertile couple.
Other assisted reproductive technologies include two modifications of the IVF technique. The first is gamete intra-fallopian transfer (GIFT), the second is zygote intra-fallopian transfer (ZIFT). In the GIFT procedure, the retrieved oocyte and sperm are mixed together and placed back into the fallopian tube where fertilization takes place. The fertilized zygote then travels down through the fallopian tube into the endometrial cavity, where implantation may or may not take place. The ZIFT procedure allows for fertilization to take place in vitro as in standard IVF, and then the fertilized zygote is placed back in the fallopian tube where it then travels down into the uterus to implant. Finally, it is becoming realized that the hyper-stimulation protocols necessary to retrieve many oocytes from the donor woman may have deleterious effects on the endometrium itself and decrease the rates of implantation. Two basic procedures have been utilized to help overcome this problem. The first is considered non-stimulated oocyte retrieval. A single egg is retrieved, allowed to be fertilized and placed back into the fallopian tube or uterus for implantation. The other technique involves the hyper-stimulation portion of the IVF procedure to retrieve the eggs and allow for fertilization in vitro. The zygotes are then frozen to be placed back into the patient after several normal cycles, with the hope that the endometrium will be more receptive to implantation. All of these techniques attempt to maximize the quality of the eggs, zygotes produced after fertilization and the receptivity of the endometrium. Any procedure which would enhance the implantation rate above the standard 15 to 20% would have a marked positive effect on any of these technologies.
There has been reported antibodies directed specifically to the Golgi complex. Smith et al., "Endogenous and monoclonal antibodies to the rat pancreatic acinar cell golgi complex", The Journal of Cell Biology, 98:2035-2046 (1984). Smith et al. disclosed immunofluorescence of tissue sections reacted with normal mouse serum demonstrated an antibody in the serum that localized to the Golgi complex area of the rat pancreatic acinar cell. The antibody is disclosed to be of IgG classes and the antigen to be an integral membrane component of the of the Golgi complex. Monoclonal antibodies (MAbs) were prepared by the authors and one MAb revealed an antigen of from about 103 to about 108 kd and the other MAb bound to two bands of 180 kd and 103 to 108 kd. The antigens are believed by the authors to be proteins.